Cardiac PDEs and crosstalk between cAMP and cGMP signalling pathways in the regulation of contractility

Abstract

Elucidation of cAMP and cGMP signalling in the heart remains a hot topic, and new regulatory mechanisms continue to appear. Studying the influence of phosphodiesterases on 5-HT4 receptor signalling in porcine atrium, a paper from this issue of the journal expands findings of a crosstalk between cardiac cGMP and cAMP signalling recently discovered in failing rat ventricle to a different species and cardiac region. The overall data suggest that cGMP, produced following stimulation of the NPR-B receptor for C-type natriuretic peptide (CNP), inhibits cAMP degradation by phosphodiesterase 3 and thereby enhances cAMP-mediated signalling from β-adrenoceptors and 5-HT4 receptors to inotropic effects. In porcine atrium, this effect can be seen both as an increase in inotropic effect and as a reduced fade of the inotropic effect with time. Thus, accumulating evidence brings together several active fields of research, including cardiac phosphodiesterases, compartmentation of cyclic nucleotide signalling and the field of natriuretic peptides. If present in human hearts, this effect of CNP may have clinical implications.